The role of CN and RH mutations in conferring antiviral drug resistance in non-B subtypes is poorly defined. We will characterize CN and RH mutations in subtype C and CRF01_AE and determine their impact on resistance to NRTIs and NNRTIs. We will genotype patients who are failing a regimen containing NNRTI therapy to determine whether the presence of CN and RH mutations can predict a higher rate of failure to AZT-containing salvage therapy. We will characterize the effects of CN mutations associated with drug resistance on viral fitness. We will determine the impact of CN mutations associated with drug resistance on viral fitness using competition assays in the presence and absence of antiviral drugs. We will dissect the mechanisms that contribute to genetic variation in CN and RH. [Corresponds to Pathak Project 2 in the April 2007 site visit report of the HIV Drug Resistance Program]